It is said that, in the drug therapy of mental diseases, maintenance therapy by continuous administration is effective in preventing recidivism of symptoms, whereby it is possible to guide patients in their daily lives. However, since the current maintenance therapy with antipsychotic drugs is carried out by orally administering tablets or fine granules once a day or dividing the daily dose into several doses per day, decreased patient compliance during the maintenance therapy causes recidivism of symptoms or re-hospitalization. Consequently, current maintenance therapy has a drawback in that certain means must be employed to improve compliance after rehabilitation or during outpatient maintenance therapy.
In order to resolve this problem, long acting injections containing drugs in the form of decanoic acid ester or enanthic acid ester have been used. For example, decanoic acid esters of haloperidol and bromperidol are disclosed in JP-A-56-8318 (the term "JP-A" as used herein means "unexamined published Japanese Patent Application"), and decanoic acid ester or enanthic acid ester of fluphenazine is also known and used in this therapeutic field.
However, these prior art long acting injections have drawbacks in that their administration route is limited to intramuscular injection, resistance at the time of administration is large because they are oil injections while the dispersibility of oil in muscular tissue is low, and their administration gives patients severe pain. In addition, there is a possibility that their effects may vary depending on individuals and their ages because, though the esters of active ingredients show a sustained release effect in the living body by gradually releasing their active moieties due to the influence of esterase, release of drugs in the living body generally depends on their transition rate from, the administered site into the lymphoid system and also on enzyme activity. Accordingly, it is desirable to develop new long acting injections in which the drugs themselves as opposed to their esters can be used.
On the other hand, each of JP-A-62-201816, JP-B-1-57087 and JP-B-2-124814 (the term "JP-B" as used herein means "examined Japanese Patent Publication") discloses sustained release microcapsules which make possible the administration of water soluble drugs at an interval of once a week or once a month, and production processes therefor. Also, JP-A-55-33414 discloses a so-called in-water drying method in which a hydrophobic drug and a polylactic acid are dissolved in a common organic solvent, the resulting solution is emulsified by adding a phase separation agent and then the solvent is removed by evaporation to obtain fine particles.
U.S. Pat. No. 4,994,281 discloses polylactic acid microspheres, prepared by the in-water drying method, containing a physiologically active substance (haloperidol, chlorpromazine, etc.) and having an average particle size of about 0.1 to 10 .mu.m.